LEO1


Description

The LEO1 (LEO1 homolog, Paf1/RNA polymerase II complex component) is a protein-coding gene located on chromosome 15.

LEO1, also known as Replicative senescence down-regulated leo1-like protein, is an enzyme that in humans is encoded by the LEO1 gene. It is a component of the PAF1 complex (PAF1C), a multi-protein complex involved in various aspects of transcription by RNA polymerase II, including transcriptional elongation, histone modifications, and mRNA processing. It is implicated in the regulation of development, maintenance of embryonic stem cell pluripotency, and leukemogenesis. PAF1C interacts with various proteins involved in transcription, histone modification, and viral infection. It associates with RNA polymerase II, interacts with histone modifying enzymes, and participates in mRNA polyadenylation. It also interacts with viral proteins, suggesting a role in viral infection.

LEO1 is a component of the PAF1 complex (PAF1C), a multi-protein complex involved in various aspects of transcription by RNA polymerase II. PAF1C plays a crucial role in regulating development and maintaining embryonic stem cell pluripotency. It associates with RNA polymerase II, interacting with its CTD (C-terminal domain) in both phosphorylated and non-phosphorylated states, and participates in transcriptional elongation. PAF1C acts independently and synergistically with TCEA1, and cooperates with the DSIF and HTATSF1 complexes. It is essential for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates the transcriptional activity of KMT2A/MLL1, an important histone methyltransferase. Additionally, it promotes leukemogenesis by associating with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL. PAF1C plays a role in histone modifications, including ubiquitination of histone H2B and methylation of histone H3 at lysine 4 (H3K4me3). It recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin, mediating monoubiquitination of lysine 120 on histone H2B (H2BK120ub1). This ubiquitination is thought to be coupled to transcription. PAF1C is also involved in mRNA 3' end formation, likely through association with cleavage and poly(A) factors. It interacts with viral NS1 protein during influenza A virus H3N2 infection, regulating gene transcription. PAF1C participates in polyadenylation of mRNA precursors and connects the PAF1 complex to Wnt signaling.

LEO1 is also known as RDL.

Associated Diseases



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